Fibrin sealants are well-established as effective hemostatic agents with numerous applications in cardiac, thoracic, plastic, and neurosurgery; skin grafting, repair of bony defects, and treatment of gastric ulcers (Gibble and Ness, 1990). The common denominator of these applications is the need for a biodegradable tissue sealant that serves to diminish bleeding or serosol leakage, or to provide additional strength to surgical anastamoses. Current fibrin sealants consist of human fibrinogen and Factor VIII derived from human plasma cryoprecipitate, and thrombin from bovine plasma (Martinowitz and Saltz, 1996). Outside the United States, commercially prepared fibrin glue kits are available which contain pasteurized human fibrinogen, bovine thrombin, and other ingredients. The FDA has not approved use of these kits due to concerns for efficacy and safety including possible viral disease risks. Therefore, U.S. surgeons frequently prepare homemade "glues". These consist of fibrinogen extracted from the patient's own plasma (autologous plasma), combined with bovine thrombin to form a glue mixture (Silver et al., 1995).
Problems with fibrin sealants now in use center on the possibility of disease transmission from both the human-derived fibrinogen from non-autologous sources, and the bovine thrombin. Recent experience in Britain linking bovine spongiform encephalopathy (BSE) and Creutzfelt-Jakob Disease in humans demonstrates the dangers of cross-mammalian infectious agents (Will et al., 1996). The dangers of viral infection from non-autologous human blood products is well known. Although various techniques are available to detect and inactivate human and other mammalian viruses, they offer relative safety only from known risks, and little if any protection from thermoresistant viruses or new infectious agents such as prions (Murphy, 1996). Also, an emerging problem with bovine thrombin is the development of antibodies to bovine blood proteins by some patients (Nichols, 1994).
The rapid clotting of blood from most teleosts (bony fish) is well-known. The mechanism is a cascade of clotting factors ending in the conversion of fibrinogen to fibrin by thrombin, similar to clotting in humans (Doolittle and Surgenor, 1962). However, these authors and others (Smit and Schoonbee, 1988; Kawatsu and Kondo, 1989) found many of the clotting proteins in fish to be species-specific. Clotting factors in fish have received little attention for human applications for several reasons. First, species-specificity of some fish plasma proteins pointed to a general incompatibility of fish and human blood proteins, discouraging further investigation. Second, only in the past few years have the dangers, both real and perceived, from human and bovine blood products been publicized. Third, until the recent establishment of commercial aquaculture, large quantities of aseptic blood of consistent composition and quality were not available.